OVERVIEW: What every practitioner needs to know

Are you sure your patient has hydrocephalus? What are the typical findings for this disease?

Hydrocephalus is a common, potentially life-threatening pediatric diagnosis that typically requires urgent surgical intervention. The immediate pathophysiology is an imbalance between the production of cerebrospinal fluid (CSF) and its absorption, typically causing clinical signs and symptoms.

The most common signs and symptoms in infants are irritability, vomiting, enlarging head circumference, tense fontanel, and sun-setting eyes. The most common signs and symptoms in older children are headache, nausea, vomiting (particularly first thing in the morning), lethargy, dysconjugate gaze, and papilledema.

Key findings

The symptoms of pediatric hydrocephalus can be quite variable. Those listed below are the most common, but in neurologically compromised children (as many who develop hydrocephalus are) the diagnosis can be difficult to make on symptoms alone. The pace of symptom development is similarly variable, with some cases progressing to coma and becoming life-threatening over the course of hours while in other cases symptoms progress over months.

Neuro-imaging is key to diagnosing hydrocephalus. Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain will always show enlargement of the ventricular system in cases of hydrocephalus and usually show the proximate cause of the hydrocephalus.

In older children (old enough to have a rigid skull - generally older than 18 months):

-Headache

-Vomiting (more common in the morning)

-Blurry vision due to papilledema - When papilledema is present, it is always caused by elevated intracranial pressure, but not all patients with elevated ICP will have papilledema. Papilledema may take weeks of elevated intracranial pressure to develop and just as long to resolve. A minority of patients (3%) do not develop papilledema due to an anatomic variant of their optic nerve sheath that does not permit CSF pressure to be transmitted to the optic nerve head.

-Dysconjugate vision (6th nerve paresis)

-Lethargy

-Coma

What other disease/condition shares some of these symptoms?

The symptoms of hydrocephalus are directly attributable to elevated intracranial pressure (ICP). Other pathologies (some listed below) that cause elevation of ICP will produce many of the same symptoms as hydrocephalus but require very different treatment. It is important to remember that many of the pathologies below can cause hydrocephalus at different points along the clinical course. Imaging is key to diagnosing hydrocephalus.

Enlargement of the ventricular system (ventriculomegaly) is the hallmark of hydrocephalus, and cranial imaging should be obtained in any patient with suspected hydrocephalus. Other conditions that can cause ventriculomegaly are listed below.

Stroke - Dying and ischemic brain tissue will swell in the days following a stroke. A large stroke is required to increase ICP.

Infection - This may include meningitis, viral encephalitis, and brain abcess.

Hepatic encephalopathy.

Reye's syndrome - much less common with the avoidance of asprin in children.

Pseudotumor cerebri - A largely idiopathic condition of elevated intracranial pressure without ventricular dilation. Typically presents in headache, papilledema, and at times, vomiting. Pseudotumor most commonly occurs in obese young adult females; however, when it does occur in children, the gender distribution is equal and it is seldom associated with obesity. Medical management (primarily with Acetazolamide) will mitigate symptoms. Most cases of Pseudotumor in children resolve spontaneously. Shunt placement is required in refractory cases.

Pathologies other than hydrocephalus that can cause ventriculomegaly

Most differential considerations for ventriculomegaly can be effectively distinguished with a good quality scan. Hydrocephalus puts outward pressure on the brain from the ventricles, typically causing compression of the sulci, sylvian fissures, and other external CSF spaces. This "tight" appearance to the brain associated with ventriculomegaly occurs only with hydrocephalus.

Pathologies other than hydrocephalus that can cause head enlargement in infants

Benign Macrocephaly (aka benign extra-axial fluid collections of infancy) - A quite common presentation to the neurosurgery clinic. Infants with benign macrocephaly have enlargement of the head that crosses percentile lines to well above the 95th percentile in the first 2 years of life. They have normal development, a family history of large heads, and a benign course. Cranial imaging shows extra-axial fluid collections and sometimes mild or moderate ventriculomegaly.

Brain tumor.

What caused this disease to develop at this time?

Most cases of hydrocephalus (particularly those presenting with acute decline) have a proximate cause readily identifiable in the patient's history or on neuroimaging. The proximate causes of hydrocephalus can be divided into 1) overproduction of CSF (very rare), 2) failure of absorption at the sagittal sinus, so called communicating hydrocephalus, or 3) failure of absorption due to obstruction of the CSF pathways, called obstructive hydrocephalus.

Communicating: Communicating hydrocephalus is the result of blood, infection, or other forms of debris in the CSF occluding the arachnoid granulations at the superior sagittal sinus. Communicating hydrocephalus sometimes resolves spontaneously.

-Post-meningitis

-Post-hemorrhagic - from subarachnoid hemorrhage, intra-ventricular hemorrhage, or germinal matrix hemorrhage of the premature infant (among the most common causes of pediatric hydrocephalus)

-Post-traumatic

-Post-surgical - commonly after resection of posterior fossa tumors

-Myelomeningocele - the pathophysiology is not entirely clear, but may be due to failure of formation of the arachnoid granulations as prenatally the CSF leaks out the spinal defect to the amniotic fluid.

Obstructive: Cerebro-spinal fluid travels a tortuous route from its production primarily in the lateral ventricles through the foramina of Monro to the third ventricle, down the aqueduct of Sylvius to the fourth ventricle, out the foramina to the posterior fossa and through the subarachnoid spaces to its absorption at the arachnoid granulations of the sagittal sinus.

-Aqueductal stenosis - a congenital defect.

-X-linked hydrocephalus - a form of aqeductal stenosis effecting males associated with adducted thumbs, mental retardation and spasticity. Caused by a defect of the gene encoding L1, a neuronal adhesion molecule mapped to the X chromosome at q28.

-Intra-ventricular or posterior fossa tumor.

-Tectal glioma - Very low grade tumors of the tectal plate that obstruct the aqueduct of sylvius.

-Colloid cyst - Rare lesion that occurs at the foramen of monro obstructing the outlet of both lateral ventricles.

-Dandy-Walker malformation.

Anatomy and physiology of CSF production, circulation, and absorption

Adults produce about 0.3 mL per minute of CSF, about 300 mL per day, a rate that shows little or no change in the presence of elevated ICP. CSF is produced from two sources - from the choroid plexus within the ventricles and from the brain parenchyma from whence it passively flows into the ventricles. CSF travels a circuitous route through the ventricles to the posterior fossa. From there it enters the subarachnoid space and can travel over the surface of the spine or the surface of the brain. CSF is absorbed primarily at the arachnoid granulations of the superior sagittal sinus.

The choroid plexus is a frond-like structure that projects into the ventricles. It produces CSF in an energy-dependent process from the blood flowing through its extensive capillary network. A small amount of choroid plexus clings to the roof of the third ventricle and another small patch hangs from the roof of the fourth ventricle, extending laterally out the foramina of Luschka, but the majority of the choroid plexus resides in the lateral ventricles. The temporal horns of the lateral ventricles have choroid plexus emerging in a band along their inferior-medial surface. This band of plexus extends around the trigones and forward through the bodies of the lateral ventricles to the foramina of Monro.

The other source of CSF is extracellular fluid of the brain parenchyma (the brain has no lymphatics). This accounts for 20-50% of CSF production. This fluid travels passively toward the ventricles and crosses the ependyma to become CSF.

Both sources of production deposit the great majority of CSF in the lateral ventricles with much smaller portions in the third and fourth ventricles. From the lateral ventricles, CSF must travel through the narrow but short opening of the foramina of Monro to the third ventricle. Obstruction at the level of the foramen of Monroe can cause a trapped lateral ventricle. To move from the third to the fourth ventricle, CSF travels through the midbrain in the aqueduct of Sylvius. This long, thin channel is prone to obstruction from congenital and acquired causes.

CSF exits the fourth ventricle through the laterally placed, paired foramina of Luschka and the midline foramen of Magendie. The CSF is now in the posterior fossa subarachnoid space which is in continuity with the lumbar and supratentorial subarachnoid spaces. Pathology in the supratentorial subarachnoid spaces (primarily the basilar cisterns) such as blood or infection can occlude passage of the CSF to the convexity where it is absorbed.

What laboratory studies should you request to help confirm the diagnosis?

No laboratory studies can confirm the diagnosis of hydrocephalus.

Would imaging studies be helpful? If so, which ones?

Imaging is the key element in diagnosing hydrocephalus. Ventriculomegaly is present in virtually all cases of pediatric hydrocephalus. Ventricles of normal or small size rule out the diagnosis of hydrocephalus, but elevated intracranial pressure may still be present from another cause.

Computed tomography (CT): CT scans of the brain are widely available, including in the middle of the night in medium and large-sized hospitals. The scan takes a few minutes and does not require sedation. This is the imaging study of choice in an emergent situation (acute change in mental status) and for the unstable patient. CT will give a good picture of the ventricles but less detail of the brain parenchyma than a full MRI. The CT does give a small dose of radiation.

Magnetic resonance imaging (MRI): A full MRI takes 45 - 90 minutes and requires the patient to be still during image acquisition. This means that most children under 7 years-old will require sedation (typically with supervision by an anesthesiologist). In many hospitals, the MRI is not staffed at night or on weekends so that an emergent scan may take hours to obtain. The MRI will examine the brain tissue in multiple ways and with far better resolution than a CT scan. The MRI gives the best chance of fully understanding any pathology underlying a new diagnosis of hydrocephalus. Contrasted scans should be performed when tumor or infection are suspected.

Quick MRI: Recently, many children's hospitals have been performing single sequence MRIs (typically a heavily T2 weighted turbo-spin echo sequence). This scan takes only a few minutes and provides an adequate picture of the ventricles and other CSF spaces. Sedation is not needed and there is no radiation exposure, but the imaging gives much less detail than a full MRI and a little less detail than a CT.

Ultrasound: Ultrasound of the head requires an open fontanel as the skull obscures everything underlying. Ultrasound provides a serviceable picture of the ventricles and some picture of the brain. It is useful particularly in the neonatal ICU setting as the study can be done at the patient's bedside eliminating the need to transport a fragile and often unstable baby.

Direct Measurement of Intracranial Pressure: In cases where data are conflicting, direct measurement of the CSF pressure or intracranial pressure is sometimes employed.

Lumbar Puncture: A lumbar puncture is the least invasive direct measure of the CSF pressure. A spinal needle is introduced into the lumbar CSF space and the fluid column height is measured with a manometer. The great disadvantage of this test is that it gives a brief measure of ICP under conditions that may physiologically alter the ICP. Such conditions include increased intra-thoracic pressure as with crying, bearing down, or positive pressure ventilation. Hyperventilation (as with crying) will also transiently decrease the ICP. Anesthetic agents have variable effects on ICP.

Rarely, a lumbar puncture in a patient with CSF obstruction or a posterior fossa mass can cause downward herniation of the posterior fossa contents with catastrophic results. Lumbar puncture should be avoided if pressure in the posterior fossa is suspected.

ICP Monitor: Several devices have been developed to monitor ICP. Most consist of a strain gauge that is zeroed to atmospheric pressure then placed inside the cranium, either in the white matter, the subdural space, or the epidural space. Such devices give continuous monitoring of the ICP allowing for assessment of pressure changes that might correspond to sleep, activity, symptoms, etc.

External Ventricular Drain (EVD): An EVD is essentially a temporary shunt. It consists of a catheter placed through a scalp incision into the ventricle connected to a collection bag which hangs at the patient's bedside. ICP can be transduced through the EVD tubing. This procedure allows for temporary treatment of the hydrocephalus as well as longitudinal monitoring of the intracranial pressure and CSF content. An EVD is commonly chosen as the initial treatment for hydrocephalus caused by another active illness (eg intracranial bleeding, infection, tumor, etc) because it allows for close monitoring and it can be easily removed if the hydrocephalus resolves.

An EVD must be leveled carefully in relation to the patient's head. If the drainage bag is placed too low, fluid will siphon out of the ventricles potentially causing intracranial bleeding. If the bag is placed too high or left clamped, intracranial pressure may rise to a dangerous level. A patient with an EVD must be cared for in a nursing unit familiar with the device, in many hospitals all EVDs are managed in an ICU.

Confirming the diagnosis

An endoscopic third ventriculostomy success score has been developed to assist in making the treatment decision between ETV and shunt placement and is contained in references at the end of the chapter. The score assigns points for age, etiology of hydrocephalus, and previous treatment with a shunt. Points are added to estimate the percentage success for third ventriculostomy. For example, a very favorable candidate who is older than 10 years, has aqueducatal stenosis and no prior shunt would have an ETV success score of 90%. The ETV success score has been tested on two large populations of children with hydrocephalus in addition to the population that was used to develop the algorithm. All showed that its reliability is good.

If you are able to confirm that the patient has hydrocephalus, what treatment should be initiated?

Hydrocephalus requires urgent surgical treatment. Very often, the first step in this treatment is placement of an external ventricular drain (EVD), a tube placed into the cerebral ventricle that drains CSF to a bag at the patient's bedside. This allows for close monitoring of CSF output, easy evaluation of the CSF (eg., cultures to follow an infectious process), and continuous monitoring of the intracranial pressure. Permanent surgical solutions for hydrocephalus include shunt placement, endoscopic third ventriculostomy, or removal of the proximate cause (eg., the case of a tumor obstructing CSF flow).

Emergent Medical Interventions:

In a child with acute, profound neurologic decline, consideration must first be given to systemic support - airway, breathing and circulation. An acute increase in the intracranial pressure can produce vomiting and stupor. Intubation is often necessary in this setting.

Mannitol: Mannitol is an osmotic diuretic that does not cross the blood brain barrier. It will pull interstitial fluids from the brain tissue into the vasculature, thereby shrinking the brain and decreasing ICP. Mannitol takes effect in about 10 minutes and typically works for about 6 hours.

Dose: 0.5-1 GM/KG IV bolus.

Precautions: Mannitol is a diuretic and may dehydrate the patient. Renal failure has been reported in dehydrated patients after prolonged mannitol use. Serum osmolarity should be monitored and mannitol should be discontinued if the osmolarity is above 320.

Hypertonic Saline: Concentrated saline (usually 3% NaCl, but sometimes 6% or 24%) will have a similar magnitude and timing of efficacy to mannitol. The mechanism of action is likewise thought to be primarily osmotic, pulling interstitial water from the brain parenchyma. Unlike mannitol, hypertonic saline is a volume expander.

Dose: 1 - 3 mL/KG as a bolus.

Precautions: Hypertonic saline can sclerose veins and in most institutions is only given through a central line. High sodium can potentiate renal damage. Hypertonic saline should be discontinued if the Na is greater than 160.

Hyperventilation: Hyperventilation will acutely decrease intracranial pressure by constricting brain arterioles. This should be employed only in dire circumstances where a more definitive intervention will be accomplished within 30 minutes.

Avoiding hypoventilation is beneficial and should always be done.

Precautions: The effect will last less than an hour, and some believe that the decreased blood flow is more detrimental than the benefit of lowering ICP.

External Ventricular Drain (EVD): An EVD is essentially a temporary shunt. It consists of a catheter placed through a scalp incision into the ventricle connected to a collection bag which hangs at the patient's bedside. ICP can be transduced through the EVD tubing. This procedure is an excellent choice in the acute setting as it allows for temporary treatment of the hydrocephalus, longitudinal monitoring of the intracranial pressure and CSF content, convenient assessment of whether hydrocephalus has resolved, and easy removal. An EVD is commonly chosen as the initial treatment for hydrocephalus caused by another active illness (eg intracranial bleeding, infection, tumor, etc).

Precautions: An EVD must be leveled carefully in relation to the patient's head. If the drainage bag is placed too low, fluid will siphon out of the ventricles potentially causing intracranial bleeding. If the bag is placed too high or left clamped, intracranial pressure may rise to a dangerous level. A patient with an EVD must be cared for in a nursing unit familiar with the device. In many hospitals all EVDs are managed in an ICU.

Shunt: Shunts are by far the most common long-term hydrocephalus treatment. A shunt allows fluid to flow from the ventricles to another space within the body (peritoneum, vasculature, pleura, etc) where it can be absorbed. The shunt consists of a ventricular catheter, a valve, and a distal catheter. The ventricular catheter is a narrow (usually between 1 and 2 mm) flexible piece of silastic tubing placed through the skull into the ventricle. Holes along the tip of the catheter allow CSF to enter. The distal catheter is a similar silastic tubing of greater length that is tunneled subcutaneously and placed into the site of distal drainage, usually the peritoneum. A shunt valve is positioned in continuity with the proximal and distal tubing. The valve provides some resistance to CSF flow through the shunt to help prevent too much drainage.

Endoscopic third ventriculostomy (ETV): More recently, endoscopic third ventriculostomy has emerged as an alternative to shunting in many instances. The procedure creates an opening in the floor of the third ventricle to allow egress of CSF to the pre-pontine cistern and from there to the remainder of the subarachnoid space. This is accomplished by placing an endoscope into a lateral ventricle from a frontal scalp incision. The endoscope is then navigated under visualization through the foramen of Monro into the third ventricle. The floor of the third ventricle just in front of the brainstem and mammillary bodies is typically thin and translucent. An instrument passed down a channel in the endoscope is used to puncture this membrane, thereby creating a new pathway for CSF circulation.

Cases of hydrocephalus caused by obstruction of the third ventricle outflow (the aqueduct of Sylvius) or obstruction of flow in the posterior fossa are ideal candidates for ETV. The procedure provides a short-cut around these portions of the CSF circulation pathway.

Types of shunts

Ventriculo-Peritoneal Shunt: The peritoneum is the preferred site of distal shunt placement in virtually all situations. The peritoneum has a large absorptive capacity that is overwhelmed only in very rare cases. Additionally, a significant length of distal catheter can be placed into the peritoneum preventing the catheter from backing of this space out as the child grows.

Contraindications to peritoneal shunt placement include an ongoing intra-abdominal infection and extensive scarring of the intra-peritoneal space. The latter condition can cause the shunt catheter to be loculated in a small space that lacks the capacity to absorb the drained CSF.

Ventriculo-Atrial Shunt: Placing the distal shunt into the right atrium is accomplished by accessing the internal jugular or subclavian vein then feeding the catheter down the vascular system. Atrial catheters are prone to two unique sources of malfunction. Thrombus can form on the catheter tip occluding the shunt. Placement within the right atrium rather than the superior vena cava or other proximal vein reduces this risk. Atrial catheters can also malfunction by backing-out of the vascular system as the child grows.

Atrial shunts can additionally thrombose or sclerose the vein in which they have been placed. If a child has had multiple atrial shunt revisions or other vascular procedures (eg central line) accessing the vascular system may be difficult. Shunt nephropathy is a rare complication unique to atrial shunts where kidney failure is caused by a low-grade shunt infection chronically depositing immune complexes into the blood stream.

Ventriculo-Pleural Shunt: The pleura has some absorptive capacity and is an option for distal shunt placement in older children (over 4 years) with reasonable pulmonary reserve. A functioning pleural shunt will always produce some amount of pleural effusion.

Occasionally, more exotic distal shunt locations are employed if all of the preceding options are contra-indicated. Such locations may include the gall bladder, the superior sagittal sinus, or the ureter.

What are the adverse effects associated with treatment for this disease?

Shunt complications

Shunt malfunction - The vast majority of children who require shunt placement are dependant on their shunt for the rest of their lives. Unfortunately, shunt malfunction is a relatively common occurrence. About 30% of shunts will malfunction in the first year following shunt placement or revision. The rate drops to about 5% per year after that first year. A shunt malfunction can have various presentations, but typically will cause headache, vomiting, then progressive decline in level of consciousness. Shunt malfunctions are life-threatening and require urgent surgical exploration of the shunt and replacement of the malfunctioning components.

Shunt infection - Shunts are particularly prone to infection. In part this is related to the silastic material from which they are made. Many bacteria are capable of forming a biofilm on the silastic that is impenetrable to the immune system and antibiotics. Shunt infections cannot be cleared without removing the shunt and treating with antibiotics for a time before placing a new shunt.

The rate of shunt infection following any surgery on the shunt is typically reported between 5 and 10%. Shunt infections related to recent surgery most commonly present within the first 6 weeks, but can occasionally be delayed as much as 6 months if the infecting organism is particularly indolent. Teenagers are at increased risk of Propionibacterium Acnes infections, an indolent organism that may take as long as 10 days to grow in culture.

Shunts can also become secondarily infected, for example from a peritonitis in the case of a peritoneal shunt or bacteremia in the case of an atrial shunt.

ETV complications

ETV failure - An ETV may fail to relieve hydrocephalus either by closure of the hole that is created in the floor of the third ventricle or if the CSF absorption mechanisms are dysfunctional. Acute failure of an ETV will commonly present with CSF leaking through the surgical site. More delayed presentations (after the scalp has healed) may present with recurrence of the hydrocephalus symptoms. On occasion, repeated ETV is attempted to re-open a healed ostomy. The success rate of this procedure is significantly lower than an initial ETV. ETV failure after 6 months is quite rare, a significant advantage over shunting procedures.

The likelihood that an ETV will succeed has been linked to several factors. The most important of these is age. Infants have a very low success rate with the procedure, and increasing age increases the likelihood of success. The etiology of hydrocephalus also has a significant correlation with success. The presence of a shunt slightly decreases the success rate.

What are the possible outcomes of hydrocephalus?

Hydrocephalus is very effectively treated with shunt placement; however, shunts are prone to malfunction requiring surgical revision (See 'Adverse effects'). Most patients who require shunt placement need a functioning shunt for the remainder of their life. Occasionally, a patient will out-grow their hydrocephalus or the process that caused hydrocephalus will resolve (eg., hemorrhage). Very few of these patients will undergo shunt removal as most are asymptomatic and determining that a shunt no longer works is imprecise and invasive.

What causes this disease and how frequent is it?

Hydrocephalus is the most common condition treated by pediatric neurosurgeons, in part due to the propensity for shunts to malfunction. The prevalence of hydrocephalus is not well known, and likely varies significantly in different socio-economic climates. Congenital and infantile hydrocephalus has been estimated at 0.48 to 0.81 per 1000 live births in the United States.

What complications might you expect from the disease or treatment of the disease?

What are the adverse effects associated with treatment for this disease?

How can hydrocephalus be prevented?

A variety of underlying diseases cause hydrocephalus, complicating efforts at prevention. Advances in medical care have recently decreased the rate of hydrocephalus development from two common causes, myelomeningocele and premature birth.

Myelomeningocele - Prenatal closure of myelomeningocele has become possible in recent years. This is accomplished by opening the uterus, operating on the fetus to close the spinal defect, then continuing the pregnancy. A randomized trial of this treatment proved quite successful in reducing the rate of hydrocephalus in children with myelomeningocele. The follow-up from the trial has been short as of this writing, and the fetal surgery is possible at only a few specialized centers, but this therapy holds promise.

Premature birth - Premature infants are prone to intraventricular hemorrhage that may lead to post-hemorrhagic hydrocephalus. For several decades, the rate of intraventricular hemorrhage has been on the whole steady. During this time, neonatal care has been improving, decreasing the likelihood of hemorrhage in the less premature infants, but also allowing smaller babies to survive (currently, infants as young as 24 weeks gestation are potentially viable). In recent years, neonatal care has advanced to the point that the rates of ventricular hemorrhage and hydrocephalus are decreasing in premature infants despite aggressive care of very premature babies.

Ongoing controversies regarding etiology, diagnosis, treatment

The value of treating hydrocephalus is well established. There has been some controversy over the past years over when an endoscopic third ventriculostomy should be attempted, but with the introduction and validation of the ETV success score our understanding of this issue is greatly advanced.

Some controversy persists about the value of many newer types of shunt implants. Several manufacturers now produce shunt tubing impregnated with antibiotics that leach out over time. Many reports have shown decreased infection rate compared with historical controls, but no definitive study has justified the cost. Dozens of shunt valves are available, without any clear evidence of different performance among them.